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epilepsy and neonatal hypoxia

Jason A Justice, Russell M Sanchez
Hypoxic-ischemic encephalopathy (HIE) refers to acute brain injury that results from perinatal asphyxia. HIE is a major cause of neonatal seizures, and outcomes can range from apparent recovery to severe cognitive impairment, cerebral palsy, and epilepsy. Acute partial seizures frequently aid in indicating the severity and localization of brain injury. However, evidence also suggests that the occurrence of seizures further increases the likelihood of epilepsy in later life regardless of the severity of the initial injury...
2018: Methods in Molecular Biology
Julie A Wixey, Hanna E Reinebrant, Kirat K Chand, Kathryn M Buller
It has become increasingly evident the serotonergic (5-hydroxytryptamine, 5-HT) system is an important central neuronal network disrupted following neonatal hypoxic-ischemic (HI) insults. Serotonin acts via a variety of receptor subtypes that are differentially associated with behavioural and cognitive mechanisms. The 5-HT7 receptor is purported to play a key role in epilepsy, anxiety, learning and memory and neuropsychiatric disorders. Furthermore, the 5-HT7 receptor is highly localized in brain regions damaged following neonatal HI insults...
March 2018: Neurochemical Research
Raymond Dunn, Bridget N Queenan, Daniel T S Pak, Patrick A Forcelli
Animal models are valuable tools for screening novel therapies for patients who suffer from epilepsy. However, a wide array of models are necessary to cover the diversity of human epilepsies. In humans, neonatal hypoxia (or hypoxia-ischemia) is one of the most common causes of epilepsy early in life. Hypoxia-induced seizures (HS) during the neonatal period can also lead to spontaneous seizures in adulthood. This phenomenon, i.e., early-life hypoxia leading to adult epilepsy - is also seen in experimental models, including rats...
February 2018: Epilepsy Research
Tamara Yawno, Suzie L Miller, Laura Bennet, Flora Wong, Jonathan J Hirst, Michael Fahey, David W Walker
Neonatal seizures are amongst the most common neurologic conditions managed by a neonatal care service. Seizures can exacerbate existing brain injury, induce "de novo" injury, and are associated with neurodevelopmental disabilities in post-neonatal life. In this mini-review, we present evidence in support of the use of ganaxolone, a GABA(A) agonist neurosteroid, as a novel neonatal therapy. We discuss evidence that ganaxolone can provide both seizure control and neuroprotection with a high safety profile when administered early following birth-related hypoxia, and show evidence that it is likely to prevent or reduce the incidence of the enduring disabilities associated with preterm birth, cerebral palsy, and epilepsy...
2017: Frontiers in Cellular Neuroscience
Megan N Huizenga, Evan Wicker, Veronica C Beck, Patrick A Forcelli
OBJECTIVE: Although drugs targeting the cannabinoid system (e.g., CB1 receptor agonists) display anticonvulsant efficacy in adult animal models of seizures/epilepsy, they remain unexplored in developing animal models. However, cannabinoid system functions emerge early in development, providing a rationale for targeting this system in neonates. We examined the therapeutic potential of drugs targeting the cannabinoid system in three seizure models in developing rats. METHODS: Postnatal day (P) 10, Sprague-Dawley rat pups were challenged with the chemoconvulsant methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) or pentylenetetrazole (PTZ), after treatment with either CB1/2 mixed agonist (WIN 55,212-2), CB1 agonist (arachidonyl-2'-chloroethylamide [ACEA]), CB2 agonist (HU-308), CB1 antagonist (AM-251), CB2 antagonist (AM-630), fatty acid amide hydrolase inhibitor (URB-597), or G protein-coupled receptor 55 agonist (O-1602)...
September 2017: Epilepsia
Amit Agrawal, Anita Banergee
BACKGROUND: Neonatal seizures are the most common clinical manifestation of Central Nervous System (CNS) dysfunction and are associated with various neurological sequelae. There are currently no evidence-based guidelines for the management of neonatal seizures and currently used drugs such as phenobarbital, and phenytoin have limited efficacy and potential toxicities. Newer second line anticonvulsant, levetiracetam, has been used in refractory neonatal seizures despite limited data and off-label use...
October 16, 2017: Current Drug Metabolism
Jiang-Jian Hu, Xing-Liang Yang, Wen-Di Luo, Song Han, Jun Yin, Wan-Hong Liu, Xiao-Hua He, Bi-Wen Peng
Hypoxia-ischemia brain damage (HIBD) is one of prevalent causes of neonatal mortality and morbidity. Our data demonstrated that hypoxia-ischemia (HI) induced Na(+)-K(+)-Cl(-)-co-transporter 1 (NKCC1) increasing in hippocampus. Previous studies demonstrated that NKCC1 regulates various stages of neurogenesis. In this study, we studied the role of increased NKCC1 in regulating of HI-induced neurogenesis. HIBD model was established in 7days old Sprague-Dawley rat pup, and the expression of NKCC1 was detected by western blot and qPCR...
February 2, 2017: Brain Research Bulletin
Li Yang, Yu-Fen Li, Li-Yun Xu, Na Xu, Yu-Zeng Han, Jun-Lin Wang, Ji-Guo Song, Ying Hua, Li-Ping Zhu
The study reports a girl with pyridoxine-dependent epilepsy. The girl was admitted at the age of 2 years because of intermittent convulsions for 1.5 years and psychomotor retardation. She had a history of "hypoxia" in the neonatal period. At the age of 5 months recurrent epileptic seizures occurred. The child was resistant to antiepileptic drugs, and had many more seizures when she got cold or fever. She also had a lot of convulsive status epilepticus. No discharges were found during several video-EEG monitorings...
January 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Julie A Wixey, Kirat K Chand, Paul B Colditz, S Tracey Bjorkman
Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses...
June 2017: Placenta
Stephanie M Miller, Susan M Sullivan, Zoe Ireland, Kirat K Chand, Paul B Colditz, S Tracey Bjorkman
Seizures are a common manifestation of hypoxic-ischaemic brain injury in the neonate. In status epilepticus models alterations to GABAA R subunit expression have been suggested to contribute to (i) abnormal development of the GABAergic system, (ii) why seizures become self-sustaining and (iii) the development of pharmacoresistance. Detailed investigation of GABAA R subunit protein expression after neonatal hypoxia-ischaemia (HI) is currently insufficient. Using our pig model of HI and subsequent spontaneous neonatal seizures, we investigated changes in protein expression of the three predominant α-subunits of the GABAA R; α1 , α2 and α3 ...
November 2016: Journal of Neurochemistry
Eridan Rocha-Ferreira, Mariya Hristova
Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI) of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age...
2016: Neural Plasticity
Ömer Kartal, Seçil Aydınöz, Ayşe Tuğba Kartal, Taha Kelestemur, Ahmet Burak Caglayan, Mustafa Caglar Beker, Ferhan Karademir, Selami Süleymanoğlu, Mustafa Kul, Burak Yulug, Ertugrul Kilic
Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats...
August 2016: Metabolic Brain Disease
Hongyu Sun, Halvor M Juul, Frances E Jensen
Despite greater understanding and improved management, seizures continue to be a major problem in childhood. Neonatal seizures are often refractory to conventional antiepileptic drugs, and can result in later life epilepsy and cognitive deficits, conditions for which there are no specific treatments. Hypoxic and/or ischemic encephalopathy (HIE) is the most common cause for neonatal seizures, and accounts for more than two-thirds of neonatal seizure cases. A better understanding of the cellular and molecular mechanisms is essential for identifying new therapeutic strategies that control the neonatal seizures and its cognitive consequences...
February 15, 2016: Journal of Neuroscience Methods
A Zayachkivsky, M J Lehmkuhle, J J Ekstrand, F E Dudek
The relationship among neonatal seizures, abnormalities of the electroencephalogram (EEG), brain injury, and long-term neurological outcome (e.g., epilepsy) remains controversial. The effects of hypoxia alone (Ha) and hypoxia-ischemia (HI) were studied in neonatal rats at postnatal day 7; both models generate EEG seizures during the 2-h hypoxia treatment, but only HI causes an infarct with severe neuronal degeneration. Single-channel, differential recordings of acute EEG seizures and background suppression were recorded with a novel miniature telemetry device during the hypoxia treatment and analyzed quantitatively...
November 2015: Journal of Neurophysiology
Natalia Rodriguez-Alvarez, Eva M Jimenez-Mateos, Mark Dunleavy, John L Waddington, Geraldine B Boylan, David C Henshall
Seizures are common during the neonatal period, often due to hypoxic-ischemic encephalopathy and may contribute to acute brain injury and the subsequent development of cognitive deficits and childhood epilepsy. Here we explored short- and long-term consequences of neonatal hypoxia-induced seizures in 7 day old C57BL/6J mice. Seizure activity, molecular markers of hypoxia and histological injury were investigated acutely after hypoxia and response to chemoconvulsants and animal behaviour was explored at adulthood...
November 2015: Neurobiology of Disease
Eridan Rocha-Ferreira, Mariya Hristova
Hypoxic-ischemic encephalopathy (HIE) is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1-5/1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy, and cognitive disabilities. Even though the brain is considered as an immune-privileged site, it has innate and adaptive immune response and can produce complement (C) components and antimicrobial peptides (AMPs). Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain...
2015: Frontiers in Immunology
Catherine I Rousset, Fiona C Leiper, Anton Kichev, Pierre Gressens, David Carling, Henrik Hagberg, Claire Thornton
Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1-2 in every 1000 term infants and the devastating consequences range from cerebral palsy, epilepsy and neurological deficit to death. Cellular damage post insult occurs after a delay and is mediated by a secondary neural energy failure. AMP-activated protein kinase (AMPK) is a sensor of cellular stress resulting from ATP depletion and/or calcium dysregulation, hallmarks of the neuronal cell death observed after HIE. AMPK activation has been implicated in the models of adult ischaemic injury but, as yet, there have been no studies defining its role in neonatal asphyxia...
April 2015: Journal of Neurochemistry
David Fernández-López, Niranjana Natarajan, Stephen Ashwal, Zinaida S Vexler
The incidence of perinatal stroke is high, similar to that in the elderly, and produces a significant morbidity and severe long-term neurologic and cognitive deficits, including cerebral palsy, epilepsy, neuropsychological impairments, and behavioral disorders. Emerging clinical data and data from experimental models of cerebral ischemia in neonatal rodents have shown that the pathophysiology of perinatal brain damage is multifactorial. These studies have revealed that, far from just being a smaller version of the adult brain, the neonatal brain is unique with a very particular and age-dependent responsiveness to hypoxia-ischemia and focal arterial stroke...
June 2014: Journal of Cerebral Blood Flow and Metabolism
Barbara Plecko, Karl Paul, Philippa Mills, Peter Clayton, Eduard Paschke, Oliver Maier, Oswald Hasselmann, Gudrun Schmiedel, Simone Kanz, Mary Connolly, Nicole Wolf, Eduard Struys, Sylvia Stockler, Lucia Abela, Doris Hofer
OBJECTIVE: To determine whether patients with pyridoxine-responsive seizures but normal biomarkers for antiquitin deficiency and normal sequencing of the ALDH7A1 gene may have PNPO mutations. METHODS: We sequenced the PNPO gene in 31 patients who fulfilled the above-mentioned criteria. RESULTS: We were able to identify 11 patients carrying 3 novel mutations of the PNPO gene. In 6 families, a homozygous missense mutation p.Arg225His in exon 7 was identified, while 1 family was compound heterozygous for a novel missense mutation p...
April 22, 2014: Neurology
Gülin Oz, Jeffry R Alger, Peter B Barker, Robert Bartha, Alberto Bizzi, Chris Boesch, Patrick J Bolan, Kevin M Brindle, Cristina Cudalbu, Alp Dinçer, Ulrike Dydak, Uzay E Emir, Jens Frahm, Ramón Gilberto González, Stephan Gruber, Rolf Gruetter, Rakesh K Gupta, Arend Heerschap, Anke Henning, Hoby P Hetherington, Franklyn A Howe, Petra S Hüppi, Ralph E Hurd, Kantarci Kantarci, Dennis W J Klomp, Roland Kreis, Marijn J Kruiskamp, Martin O Leach, Alexander P Lin, Peter R Luijten, Malgorzata Marjańska, Andrew A Maudsley, Dieter J Meyerhoff, Carolyn E Mountford, Sarah J Nelson, M Necmettin Pamir, Jullie W Pan, Andrew C Peet, Harish Poptani, Stefan Posse, Petra J W Pouwels, Eva-Maria Ratai, Brian D Ross, Tom W Scheenen, Christian Schuster, Ian C P Smith, Brian J Soher, Ivan Tkáč, Daniel B Vigneron, Risto A Kauppinen
A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system...
March 2014: Radiology
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